Nucleic acid secondary structures containing the double-headed nucleoside 5'(S)-C-(2-(thymin-1-yl)ethyl)thymidine.
Oligodeoxynucleotides containing the double-headed nucleoside 5'(S)-C-(2-(thymin-1-yl)ethyl)thymidine were prepared by standard solid phase synthesis. The synthetic building block for incorporating the double-headed moiety was prepared from thymidine, which was stereoselectively converted to a protected 5'(S)-C-hydroxyethyl derivative and used to alkylate the additional thymine by a Mitsunobu reaction. The oligodeoxynucleotides were studied in different nucleic acid secondary structures: duplexes, bulged duplexes, three-way junctions and artificial DNA zipper motifs. The thermal stability of these complexes was studied, demonstrating an almost uniform thermal penalty of incorporating one double-headed nucleoside moiety into a duplex or a bulged duplex, comparable to the effects of the previously reported double-headed nucleoside 5'(S)-C-(thymin-1-yl)methylthymidine. The additional base showed only very small effects when incorporated into DNA or RNA three-way junctions. The various DNA zipper arrangements indicated that extending the linker from methylene to ethylene almost completely removed the selective minor groove base-base stacking interactions observed for the methylene linker in a (-3)-zipper, whereas interactions, although somewhat smaller, were observed for the ethylene linker in a (-4)-zipper motif.
Andersen
Charlotte
C
Nucleic Acid Center, Department of Chemistry and Physics, University of Southern Denmark, 5230 Odense M, Denmark.
Sharma
Pawan K
PK
Christensen
Mikkel S
MS
Steffansen
Signe I
SI
Madsen
Charlotte M
CM
Nielsen
Poul
P
D001483:Base Sequence; D002244:Carbon / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry* / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C521750:5'(S)-C-(thymine-1-ylmethyl)thymidine; D009696:Nucleic Acids; D009838:Oligodeoxyribonucleotides; D002244:Carbon; D013936:Thymidine